IDE397 plus sacituzumab govitecan shows anti-tumor activity in MTAP-deletion urothelial carcinoma

IDEAYA Biosciences has announced positive updated data from their ongoing phase 1/2 trial (NCT04794699) of IDE397, an investigational small molecule adenosyltransferase 2a (MAT2A) inhibitor, in combination with sacituzumab govitecan-hziy (Trodelvy) for patients with late-line methylthioadenosine phosphorylase (MTAP)-deletion urothelial carcinoma.¹

The data include results from 19 patients enrolled across 2 dose cohorts in the study. Patients in cohort 1 (n = 9) received IDE397 at 15 mg and sacituzumab govitecan at 10 mg/kg, and patients in cohort 2 (n = 7) received IDE397 at 30 mg and sacituzumab govitecan at 7.5 mg/kg. The trial is also evaluating the combination in patients with non–small cell lung cancer and other solid tumors. 

"We are pleased with the progress we are making with the Trodelvy and IDE397 combination and are encouraged by the early response rate data we are seeing in previously treated MTAP-deleted urothelial cancer,” said Darrin M. Beaupre, MD, PhD, Chief Medical Officer of IDEAYA Biosciences, in the news release from the company.¹ “These results set the stage for further testing of the combination in non-small cell lung cancer, where we have just dosed the first patient in our clinical trial.”

In total, the efficacy evaluable population across both cohorts included 19 patients with late-line MTAP-deletion urothelial carcinoma. To be eligible for analysis, patients needed to have at least 1 post-baseline tumor assessment per RECIST v1.1. Across all patients, 68% had progressed following 2 or more prior therapies, which consisted of an immune-oncology therapy in 84% of patients (16 of 19) and enfortumab vedotin (EV) in 32% of patients (6 of 19).

Overall, data showed a disease control rate of 100% in cohort 1 (9 of 9) and 71% (5 of 7) in cohort 2. In cohort 1, the objective response rate (ORR) was 33%, which included 3 patients who achieved a confirmed partial response (cPR). The ORR in cohort 2 was 57%, including 3 patients with a cPR and 1 patient with unconfirmed partial response.

According to IDEAYA Biosciences, “The preliminary combination data is trending favorably vs historical Trodelvy monotherapy efficacy reported in metastatic UC, including 11% ORR in patients post-EV therapy (Sternschuss et al., 2025) and 23% ORR in predominantly EV-naïve patients (Powles et al., 2025).”

At the time of data report, the median progression-free survival and duration of response had not been reached in either cohort.

Safety data on IDE397 plus sacituzumab govitecan was consistent with the known safety profiles for each agent. Adverse events (AEs) were generally manageable, and no serious treatment-related AEs (TRAEs) were reported in cohort 2. The most common grade 3 or greater TRAEs were anemia and neutropenia in cohort 1 and anemia, asthenia, and diarrhea in cohort 2.

According to the IDEAYA Biosciences, the selection of a recommended phase 2 dose is planned for the end of 2025. The next data update is expected to be presented at a medical conference in the first half of 2026.

In total, the trial plans to enroll 180 patients across several solid tumor types.² To be eligible for enrollment, patients need to have an advanced or metastatic solid tumor that progressed on at least 1 prior line of therapy or is intolerant to additional effective standard therapy. Patients also need to have evidence of homozygous loss of MTAP or MTAP deletion, an ECOG performance status of less than or equal to 1, and adequate organ function.

The primary end points for the study include dose-limiting toxicities and preliminary anti-tumor activity as measured by the ORR and duration of response. Secondary end points include pharmacokinetic measures and additional efficacy assessments.

Primary completion of the trial is expected in December 2026.

REFERENCES

1. IDEAYA Biosciences announces positive data from phase 1/2 combination trial of IDE397, a potential first-in-class MAT2A inhibitor, and trodelvy in MTAP-deletion urothelial cancer. News release. IDEAYA Biosciences, Inc. September 8, 2025. Accessed September 8, 2025. https://www.prnewswire.com/news-releases/ideaya-biosciences-announces-positive-data-from-phase-12-combination-trial-of-ide397-a-potential-first-in-class-mat2a-inhibitor-and-trodelvy-in-mtap-deletion-urothelial-cancer-302548584.html

2. Study of IDE397 in participants with solid tumors harboring MTAP deletion. ClinicalTrials.gov. Last updated November 18, 2024. Accessed September 8, 2025. https://clinicaltrials.gov/study/NCT04794699